Optical techniques, including prism refractometry, interferometry, and surface plasmon resonance (SPR), have long been used for measuring optical properties of samples, such as index of refraction.
Refractometers have been used in the field of analytical chemistry for measuring the index of refraction of liquids for analytical purposes. Modern automatic refractometers determine the critical angle between transmission and total internal reflection in an optical prism of known high refractive index. At the interface between a liquid sample and a higher index prism, the critical angle θcrit is defined by sin(θcrit)=nlow/nhigh, where nhigh is the refractive index of the prism and nlow is the index of the liquid being measured. With knowledge of the refractive index of the prism, by measuring the critical angle, the index of the liquid being measured can be calculated.
Waveguide interferometry, which can measure very small shifts in interference patterns generated by minute changes in refractive index, is inherently more sensitive than prism refractometry. However, the waveguide interface to the sample is also inherently more expensive.
SPR takes advantage of the fact that at a unique narrow range of angles, a thin layer of metal does not reflect light as well as it does at other angles. In this narrow range of angles, energy is transferred from light rays striking the metal into the metal itself. The energy is transferred into the metal instead of being reflected because of the surface plasmon resonance effect. The pronounced reduction in reflection occurring at that narrow range of angles produces an attenuated band within an otherwise bright region of reflected light that shines on a detector. The narrow range of angles depends on index of refraction of a material that is on the opposite surface of the thin metal. Thus, a chemical reaction in a material on that opposite surface that changes its index can result in a shift in the narrow range of angles. This shift can be detected, providing a way to determine that a reaction occurred or to follow the reaction dynamically.
While each of these systems has been studied and used, all remain complex and expensive to use, require complex handling of materials, provide contamination issues, have required careful preparation, and/or present challenges for uses demanding high throughput.